Apparatus for extraction of drugs and toxic substances from blood, serum and other liquid

ABSTRACT

Said apparatus is housed on and in a convenient metal frame. It has three extraction chambers arranged vertically. It extracts the desired drug or toxic substance from the sample with a suitable solvent. This extraction is carried out in the upper extraction chamber, after which the solvent is filtered into the midextraction chamber, and the sample or aqueous phase is retained. The middle extraction chamber contains carbon black, some other adsorbing agent or aqueous solution which effects the purification of the solvent. The solvent is filtered a second time into the lower extraction chamber where the desired drug or toxic substance is reextracted from the solvent into an acidic or basic solution, depending on its chemical nature. The actual extractions and purification are effected by a shaking motion of the extraction chambers, and all operations (extractions, purification and filtrations) are done automatically according to a predetermined program.

D United States Patent [1113,620,681

[72] Inventor Fzle S. Wright 3,226,407 12/ 1965 Bergman .l 23/267 X14947 Clymar St., Compton, Calif. 90220 3,259,462 7/1966 Anscherlik23/259 X [2]] Appl. No. 863,892 3,348,921 10/1967 Katz 23/259 [22] FiledOct. 6, 1969 3,403,980 10/1968 Litterio 23/259 X [45] Patented Nov. 16,1971 3,415,380 12/1968 Ellis 23/259 X FOREIGN PATENTS s41 APPARATUS FOREXTRACTION or DRUGSAND 328 :33; gg z gggg Toxic SUBSTANCES FROMBLOODSERUMAND 443 232 1912 France y m 23/272 om uQUm 2 Claims, 4 DrawingFlu. Primary ExaminerNorman Yudkoff 521 US. cl. 23/267 c, EmeY 210/322ABSTRACT: Said a paratus is housed on and in a convenient P [51] Int. CLBold 11/02, metal frame It has three extraction chambers arranged veniBold 11/04 cally. lt extracts the desired drug or toxic substance fromthe [50] Field of Search 23/267, sample with a suitable solvent Thisextraction is carried out in 259, 292, 272, 312 S, 312 A, 3 l2 R, 312ME, the upper extraction chamber, after which the solvent is fil- 3] 1;210/ 322 tered into the midextraction chamber, and the sample or aqueousphase is retained. The middle extraction chamber contains carbon black,some other adsorbing agent or aqueous [56] CM solution which efi'ectsthe purification of the solvent. The sol- UNITED STATES PATENTS vent isfiltered a second time into the lower extraction R 2 ,13 611E5- aygn9gl. 231259 chamber where the desired drug or toxic substance is reex-833,573 10/1906 BecigneuL. 23/312 S tracted from the solvent into anacidic or basic solution, de- 9|2.634 2/ 1909 Warburton 210/252 Xpending on its chemical nature. The actual extractions and pul,890,93912/1932 Fahmey 23/259 rification are efi'ected by a shaking motion ofthe extraction 2,136,372 1 H1938 Burnett 23/272.5 X chambers, and alloperations (extractions, purification and fil- 2,968,721 1/1961 Shapiro23/272 X trations) are done automatically according to a predetermined3,206,276 9/1965 Bur-well 23/312 ME program.

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BY 6B4 I APPARATUS FOR EXTRACTION F DRUGS AND TOXIC SUBSTANCES FROMBLOOD, SERUM AND OTHER LIQUID BRIEF SUMMARY OF THE INVENTION Theinvention was designed to carry out many of the manual operationsinvolved in the extraction of drug or toxic substances from blood, serumor other aqueous solutions. In addition to making a more thoroughextraction, it has the capacity to complete many extractionssimultaneously and thereby save time. More specifically, it makes theextraction of the desired substance from the sample into a solvent ofchoice that is more dense than the sample. After extraction, a briefperiod is allowed for complete separation of the solvent and sample.Then the solvent is filtered and purified in a separate chamber with anadsorbing-agent or suitable solution. Next, it is separated from thepurifying agent and filtered again. Finally the desired substance isextracted from the solvent with acidic or basic solution, depending onits chemical nature, and reserved for spectrophotometric or otheranalysis. All operations mentioned are done automatically in turn by apredetermined program.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS FIG. 1 is a view of theprogrammer unit from the rear. It shows the physical arrangement of thecam and the microswitches activated by it. The programmer motor, whichdrives the cam is not shown although it is attached underneath theprogrammer shelf. Also the electrical wiring is not shown in the view.

FIG. 2 shows the side view of the extraction panel when viewed from theright side. In this view, the suspension of said panel is shown. Alsothe arrangement of the solenoids, for opening the upper and middleextraction chambers is shown. And the solenoid for opening the upperextraction chamber is not shown since it may clutter the view of theupper rocker arms.

FIG. 3 shows the front of the apparatus. It presents a view of thecontrol panel on the left, on which is mounted the programmer indicatorlamp-part 11, the master switchpart 15, the fusepart l6, and theactivator button-part 13. On the right side of the apparatus theextraction panel is obvious. It shows the three extraction chambers withfunnels fitted at the top of the lower and middle chambers. Also thesuspension of the extraction panel is shown by the attachment of therocker arms to the panel and to the frame. The rocker arms in this vieware behind the extraction panel but in front of the frame. A section ofthe frame is cut away on the right side of the apparatus to enhance theview of the shaker motor-part 10. The base of the shaker motor is alsoseen in this view. The pushrodpart 25, which is connected to the crankof the shaker motor and to the rear of the extraction panel is alsoshown.

FIG. 4 merely shows the schematic diagram of the electrical circuit.

DETAILED DESCRIPTION The detailed description of the invention isdivided into two parts:

PART 1 explains construction of the invention.

PART II explains operation of the invention.

PART I-CONSTRUCTION FRAME The above-mentioned apparatus is mounted on aframe 25 inches tall, 12 inches wide and 8 inches deep. The material ofconstruction of said frame is l l inches angle iron. Two more pieces ofsaid angle iron are attached to frame, crosswise, in front and back and6 inches up from the bottom. The purposes of these are to hold a shelfon which the programmer unit is mounted, and the front piece also servesas the base to which a moving part is attached. Said moving part will beexplained later. A piece of channel iron, 1%X% inches is attached to theframe on the left side, running depthwise, and the top side of thechannel is 9% inches below the top of the frame. The purpose of this isto serve as a motor mount for a geared electric motor whose one quarterinch shaft ends in a crank with a three-eighth inch displacement. Seepart No. 10, FIG. 3. The frame may be fastened together by bolts, rivetsor welding, preferably welding. Also, a piece of 2$ 4%Xl/l6 inchesstainless steel or aluminum is attached to the front right side of theframe in a lengthwise manner. This runs the entire length of the frame,and is referred toss the control panel. See part 26, FIG. 3. On thiscontrol panel is mounted the fuse holder (part 16, FIG. 3), theprogrammer motor indicator lamp (part 11, FIG. 3), the master switch(part 15, FIG. 3) and the activatorbutton (part 13, FIG. 3).

PROGRAMMER UNIT The programmer unit controls all the operations of theapparatus. It consists of a double pole relay (part 14, FIG. 4), a timermotor with a speed of l revolution per 30 minutes, a 3%- inch diametercam driven by the timer motor. The timer cam has a raised portion whichextends three-sixteenths inch out beyond the diameter and subtends anarc of 42. This raised portion activates the microswitches arrangedaround it, for a duration of 3% minutes each, when the timer motor is inoperation. There are six microswitches (parts I-6, FIG. 1) arrangedradially around, and each activated in turn by the programmer cam (part7, FIG. 1). All operations of the program are carried out in one 30minute revolution of the cam. The timer motor is mounted underneath theprogrammer shelf and is not shown except in the schematic diagram (seepart 12, FIG. 4). However, the shaft of said timer motor extends upwardthrough the shelf and turns the programmer cam in a clockwise direction.The overall function of the programmer unit will be covered in thedescription of operation.

EXTRACTION PANEL The extraction panel is a piece of stainless steel oraluminum 24X4% inches. (See part 24, FIGS. 2 and 3). Its purposes aretwofold:

A. it serves as a base to which'the three extraction chambers areattached, with clamps as shown, parts 18, 19, and 20, FIGS. 2 and 3. Theupper and midextraction chambers are sealed at the bottom by a rubberpoliceman mounted at the end of a spring loaded lever. Both levers arereferred to by the same part number (21 FIGS. 2 and 3. Also at theproper time in the program, each lever is activated by the solenoid(part 9, FIG. 2). The solenoid for the upper extraction chamber is notshown. When the upper extraction chamber (part 18, FIGS. 2 and 3) or themiddle extraction chamber (part 19, FIGS. 2 and 3) is opened by thesolenoid activated lever, the fluids in the chamber are permitted todrain out and into the 8 cm. funnel which is fitted with 10 cm. filterpaper. The upper extraction chamber is sealed at the top by a Teflonstopper as shown. And the middle and lower extraction chambers arefitted at the top with Teflon stoppers, each of which is bored throughand fitted with an 8 cm. funnel as shown. Each funnel shares the samepart number (23), FIGS. 2 and 3. The lower extraction chamber (part 20,FIGS. 2 and 3) is sealed at the bottom by an appropriately attachedstopcock as shown.

B. The second purpose of the extraction panel is to oscillate from rightto left or vis a vis. This oscillatory motion (240 oscillations perminute) shakes the extraction chamber which effects the extraction orwashing action as the case may be according to the program. Theextraction panel is suspended from the frame by three rocker arms, eachbeing referred to by the same part number (22), FIGS. 2 and 3. Therocker arms are steel, 4X$Xs inches, with holes drilled at each end witha distance of 2% inches between centers.

Also the rocker arms are fitted with 54-inch rivets or other suitablebearings. The upper end of each arm is fitted to the frame and the lowerend is fitted to the extraction panel. FIGS. 2 and 3 show theconnections of the rocker arms to the frame and extraction panel. Two ofthe arms are used near the top, and the third one is used near thebottom. The oscillation or shaking motion is provided by an electricmotor with a gear reduction mounted at the lefi of the frame. See part10, FIG. 3. This 240 r.p.m. motor has a one-quarter inch shaft that endsin a crank with a three-eighth inch displacement. The crank is connectedto the extraction panel, near its center of gravity, with a ZXBXifiinches pushrod (part 25, FIG. 3).

ELECTRICAL CIRCUTI The electrical circuit is shown schematically in FIG.4. The power comes through a standard 110 volt plug with a ground (part17, FIG. 4). Next, it passes through the double pole single throw masterswitch (part 15, FIGS. 3 and 4). Also a ampere fuse is incorporated intothe circuit (part 16, FIGS. 3 and 4). All operations are completed in a30 minute cycle which stops as soon as the raised portion of theprogrammer cam opens the cut ofi microswitch (part 6, FIGS. 1 and 4).This particular microswitch is a single pole double throw type. And oneof its purposes is to cut off the programmer cam motor (part 12, FIG.4). After the cam engages, it is in the position shown in FIG. 4. Tobegin the next cycle, the activator button is pushed. The activator is apush button, two point make switch, and an instantaneous touch is allthat is needed to engage the double pole, double throw relay (part 14,FIG. 4). As shown in FIG. 4, the relay is in the open position, but itis closed as soon as the activator is pushed and remains closed althoughthe activator is released. In the closed position, current passesthrough the cutoff microswitch and through the bottom pole of the relayto keep the relay coil energized. Also, in the closed position, currentpasses through the cutoff microswitch through the top pole of the relayand energizes the programmer motor (part 12, FIG. 4) and the programmerindicator lamp (part I 1, FIGS. 3 and 4). As soon as the raised portionof the programmer cam passes and disengages the eutoff microswitch, itgoes to its normally closed position which disengages the relay andenergizes the programmer motor and indicator lamp directly. Statedbriefly, the purpose of the relay and two point make pushbutton is tokeep the programmer in operation until after the cam has passed thecutoff microswitch. At this point, the raised portion of cam isapproaching the first microswitch to begin all operations of the newcycle.

Parts l,2,3,4 and 5, FIGS. I and 4 are all normally open microswitches.They are each activated by the cam in their 'tum to accomplish theautomatic operations of the program,

which are:

Microswitch (I) energizes shaker motor for 3% minutes. The microswitchesare spaced to allow an 8 minute delay between microswitches I and 2.Microswitch (2) activates the solenoid that opens the bottom of theupper extraction chamber (part 18, FIGS. 2 and 3). Microswitch (3)energizes the shaker motor for another 3 /5 minutes. Microswitch (4)activates the solenoid that opens the bottom of the middle extractionchamber (part 19, FIGS. 2 and 3). Microswitch (5) energizes the shakermotor for the third and final 3% minute period. Microswitch (6) cuts offthe programmer motor and ends the cycle.

MANUFACTURING The apparatus shown in this specification is a single unitwhich handles a single sample at a time. It is desired that thisapparatus be manufactured with multiple units combined on a singleframe. This arrangement could be effected using the same electricalcircuit and components except a motor of larger horsepower would berequired for the shaker. If manufactured in multiple unit arrangement,this apparatus would be capable of making many simultaneous extractionsin the same time required to complete a single extraction.

PART II-OPERATION A. For acidic or basic substances.

The operation begins by placing an appropriate volume of sample (2-7ml.) into the upper extraction chamber (part 18, FIGS. 2 and 3). Alsoadd to the same chamber a volume of solvent equal in size to 10 timesthe sample. The solvent must have a density greater than that of thesample. Both funnels (parts 23, FIGS. 2 and 3) are fitted with I0 cm.filter paper. A match head size portion of activated carbon is added tothe middle extraction chamber (part 19, FIGS. 2 and 3), and a finalsolution is added to the lower extraction chamber (part 20, FIGS. 2 and3). A convenient volume of final solution is 5 ml. If the drug orsubstance to be extracted from the sample is acidic in nature, then thefinal solution should be basic. If said drug or substance is basic innature, then the final solution should be acidic.

The apparatus is now ready to operate and the activator button ispushed. The first operation is the extraction panel will be shaken,which will extract the desired substance from the sample into thesolvent.

After the first extraction, an 8 minute waiting period is allowed by theprogram to permit good separation of the aqueous and solvent phases.Next, the bottom of the upper extraction chamber is opened automaticallyand the solutions drain out. The solvent, being heavier, drains first.It goes through the filter paper and into the middle extraction chamber,(part 19, FIGS. 2 and 3). Ifthe sample is blood, it will either remainin the upper extraction chamber or be caught on the filter paper. If thesample is any other aqueous solution, it will be absorbed by the filterpaper. With this in mind, ample filter paper should be used in thefunnel fitted to the middle extraction chamber.

After draining and filtration, the extraction panel will again beshaken. This is to permit the carbon black to adsorb certain impuritieswhich may be present. This particular shaking operation, as well as theother two, lasts for a duration of 3% minutes.

After shaking the bottom of the middle extraction chamber, it isautomatically opened, permitting the solvent to drain out and throughfilter paper and funnel into the bottom extraction chamber, part 20,FIGS. 2 and 3.

Next, the extraction panel is automatically shaken a third and finaltime. This shaking effects the extraction from the solvent and into thefinal solution. After the last extraction, the apparatus cuts itselfoff. After this, the solvent may be manually drained from the lowerextraction chamber (part 20, FIGS. 2 and 3) and discarded. Next, thefinal solution, containing the extracted substance, is drained out ofthe lower extraction chamber for spectrophotometric analysis or otherdisposition.

B. For Neutral Substances.

The procedure and operations for the extraction of neutral substancesare the same as for acidic and basic substances, except there is nofinal solution into which the extracted substance goes. It stays in thesolvent phase. Also in the case of neutrals, the middle and lowerextraction chambers are used to effect purification or washing of thesolvent extract. One chamber may be used to hold acid solution and theother may be used to hold basic solution, or the middle and lowerextraction chambers may be used to hold any other wash solutions orcompounds, depending on the nature of the neutral compound and thesample from which it is extracted.

C. Metal Cones.

Two metal cones are prepared to fit into the funnels after they havebeen fitted with the filter paper. Also the vertex of each cone is cutoff to permit fluid passage through the cone. A cone is fitted intoeither funnel when an aqueous solution, either wash or sample, is usedin the extraction chamber above it. The purpose of the cone is toprevent the aqueous solution from touching the filter paper until allthe solvent has gone through.

It is claimed that this invention will do two things. They are:

l. Extraction apparatus comprising three vertically serially arrangedextraction vessels, said vessels each having a top opening and a bottomopening, first and second normally closed valves in the bottom openingof the top vessel and middle vessel respectively, a valve in the bottomopening of the bottom vessel, first and second filters disposed betweenthe top and middle vessels and the middle and bottom chambersrespectively, each filter being adapted to receive material dischargedthrough the bottom opening of the vessel directly above it and todischarge filtered material through the top opening of the vesseldirectly below it, a vertical panel, said vessels, filters, and valvesbeing mounted on said panel, motor means connected to said panel toprovide oscillating shaking motion of said panel, and timer-controlmeans operatively connected with the motor means and valve means toprovide in sequence the steps of actuating the motor means to shake thepanel and mix material in the top vessel, deactuating the motor means toprovide a settling period, opening the first valve to allow material todrain out of the top vessel into the first filter and filtrate thenceinto the middle vessel, actuating the motor means, and opening thesecond valve to allow material to drain out of the middle vessel intothe second filter and filtrate thence into the bottom vessel.

2. The apparatus of claim 1, wherein the timer-control means is arrangedto provide the additional step of actuating the motor means to shake thepanel and provide mixing of the filtrate passed into the bottom vessel.

l i i i i

2. The apparatus of claim 1, wherein the timer-control means is arrangedto provide the additional step of actuating the motor means to shake thepanel and provide mixing of the filtrate passed into the bottom vessel.